DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Drawings
The drawings are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims.
Therefore, the “limit groove” of Claims 5 and 12 must be shown or the feature(s) canceled from the claim(s). No new matter should be entered.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Interpretation
Regarding Claim 8, the claim recites “method for sorting fluorescently labeled cells by the microfluidic chip device based on the magnetic field-controlled fluorescently labeled cell sorting method” wherein the claim is interpreted as positively requiring the providing of the device of Claim 1. If this is Applicant’s intent, Applicant may wish to amend the claim with a positive method step on the order of “providing the device of Claim 1”.
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier.
Such claim limitation(s) is/are:
a magnetic field control system for controlling the magneton, as in Claim 1.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
Opposing magnets on opposite sides of the sorting channel...as in para. [0034] and fig. 1 of Applicant’s instant specification...and equivalents thereof, however, further clarification is required.*
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
As discussed above, “magnetic-field control system for controlling the magneton to move…” is interpreted under 35 USC 112 F/6th as an alternative-type “means for” recitation, wherein, as best understood herein, the coincident structure(s) is given as the opposing magnets as in par.[0034] and fig .1.
However, magnets alone do not provide for control and as such the metes and bounds of the structure(s) to the magnetic-field control system are indefinitely defined.
It is unclear what additional elements to the magnets are provided that impart a control functionality so as to selectively impart a magnetic field to the system.
Examiner notes that par.[0019] generally discloses that the magnetic field control system is turned on, however, there is no particular discussion as to the infrastructure/mechanism that provides for this aspect.
It is also noted that the disclosure does not appear to provide a mechanical mechanism for moving the magnets 110 within the confines of the device so as to impart a controlled aspect to the spatial designation of the applied magnetic field.
By this, further clarification is required as to the structural correspondence of the claimed magnetic-field control system for its recited functionalities as claimed.
Claim 1 recites “a microfluidic chip device based on a magnetic field-controlled fluorescently labeled cell sorting method” wherein it is unclear from this recitation what constitutes the relationship between the device and the method based on the “based on” recitation. Therein, it is unclear which statutory category of invention Applicant intends, given that Claim 1 recites both a device and a method.
Applicant is invited to clearly define the statutory class of invention sought and the positively recited elements given thereto.
Similarly as above, Claim 8 recites “method for sorting fluorescently labeled cells by the microfluidic chip device based on the magnetic field-controlled fluorescently labeled cell sorting method” wherein it is even further unclear the relationship between the device and the method given that the method here is recites as based on a device based on a method.
Applicant should make clear the positively claimed steps/elements of the preamble as the microfluidic chip or a method performed using the microfluidic chip.
Herein, it appears that Applicant intends to provide an initial step to –
-providing the microfluidic chip as in claim 1
This would definitively establish the active steps of the methodology being practiced in accordance with the structure of the microfluidic chip of claim 1 as appears inferred, but not clear given the present reference residing in the “based on…” clause within the preamble of claim 8.
Claim 1 recites the limitation "the cell sorting area". There is insufficient antecedent basis for this limitation in the claim. Applicant may wish to amend the claim to recite “the magnetic field-controlled cell sorting area”.
Claim 1 recites “a magnetic field-controlled cell sorting area” wherein this element is described narratively and it is thereby unclear if the element requires a magnet, control system, or specific volume. As currently recited, the “area” is merely a designated region of space and will be construed accordingly for purposes of examination.
Claims 3 and 10 recite the limitation "the same structure". There is insufficient antecedent basis for this limitation in the claim. Applicant may wish to amend the claim to recite “a same structure” or remove the recitation and allow the “each comprising” recitation to refer to the first and second fluorescent detection areas.
Claim 8 recites “a detection result is processed by a computer system and then fed back to the magnetic field control system controlled by the computer system” wherein it is unclear if the “computer system” performing operations is a separate computer from the magnetic field control system. Note that the 35 USC 112(f) interpretation, as discussed above in the Claim Interpretation section, interprets the magnetic field control system as a computer based on its being “controlled by” a computer system. By this, if the computer system and magnetic field control system are actually separate elements, the magnetic field control system would be indefinite for failing to provide sufficient structure to the generic placeholder of the magnetic field control system.
Further, the term “magneton” in Claims 1, 5, 8, and 12 (and dependents thereof) is not a recognized term of art. The claim recitations therewith are drawn to interaction with a magnetic-field control system, but it is unclear through Applicant’s specification what constitutes a “magneton.”
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999).
Clarification is required as to what is meant by “magneton.”
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 5-9, and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Chiu et al. (US 2020/0206740 A1), hereinafter “Chiu”, in view of Chang-Yen et al. (US 2011/0127222 A1), hereinafter “Chang-Yen”.
Regarding Claim 1, Chiu teaches a microfluidic chip device based on a magnetic field-controlled fluorescently labeled cell sorting method, wherein the microfluidic chip comprises:
a sample channel (Fig. 1A shows a sample channel labeled with “sample in”.),
two sheath fluid channels (Fig. 1A shows two sheath fluid channels both labeled with “buffer in”.),
a first fluorescence detection area, a second fluorescence detection area ([0174]: “The first detection window can have two laser beams simultaneously overlapping and can be used detect the fluorescence signals from the labeled rare cells (e.g., CTCs). The second detection window can be used to confirm the identity of the rare cells, or lack of rare cells, in the sorted aliquots. The second detection window can further be used to monitor the sorting efficiency.” – Examiner further notes that the “areas” claimed merely require an arbitrary designation in space not tied to any specific structure of the device, such that any area of the device capable of performing fluorescence measurements is interpreted as such an “area”, and that, for example, a single fluorescence detection chamber could comprise two separate “areas” arbitrarily designated by one having ordinary skill in the art.),
a magnetic field control system ([0020]: “a computer comprising a processor and a non-transitory memory with executable instructions stored thereon, which when executed by the processor cause the apparatus to: operate the detector to detect a first presence of the particle in a first aliquot of the sample; operate the valve to direct the flow of the first aliquot to a first volume to form a first isolated sample upon detecting the presence of the particle in the first aliquot; direct the first isolated sample to the dispersion stage to form a dispersed sample; and perform a separation procedure on the dispersed sample.” – As the device of Chiu utilizes magnetic fields to perform a separation procedure, such as discussed in paras. [0147, 0164, 0239], the controller/computer is interpreted as a magnetic field control system herein.)
a magnetic field-controlled cell sorting area (See “sorting stage” as in paras. [0208-0216] and note “the mechanism for sorting comprises...a magnetic element” in para. [0117] – see also Fig. 18A “Second Sorting Stage”.),
a target cell channel (Figs. 1A and 18A show thew target cell channel(s) as branching to the left (below the sheath buffer channels) and the waste channel(s) branching to the right. Cells/analytes passing through the target cell channel move on to further analysis as in Fig. 1A or further sorting/refinement as in Fig. 18A.),
and a waste fluid channel (Figs. 1A and 18A show the waste channel(s) designated as “waste out”.);
wherein the sample channel communicates with the two sheath fluid channels, the sample channel and the two sheath fluid channels are connected in parallel with each other, and the sample channel is located between the two sheath fluid channels (Fig. 1A shows the sample channel in fluid communication with the two sheath fluid channels, the two sheath fluid channels are arranged/connected parallel to one another, and the sample channel is between the two.);
pipelines for connecting the sample channel and the two sheath fluid channels are a first flow channel and a second flow channel respectively; the first flow channel and the second flow channel intersect with the two sheath fluid channels at a first intersection point and a second intersection point respectively; the target cell channel starts from the first intersection point, and the waste fluid starts from the second intersection point (See the annotated Fig. 1A below. Note that target cells are shown as flowing through the first flow channel and waste is shown as flowing through the second flow channel.);
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the magnetic field-controlled cell sorting area is provided on the first flow channel and the second flow channel (Given the flow switching shown in Figs. 9A-C, as well as the general knowledge available to one of ordinary skill in the art that magnetic aqueous cell/particle separations are attractive in nature (magnetically-labelled cells/beads are attracted to a magnetic field generator), wherein the separation shown in Fig. 9A-C would not thereby be achievable unless the magnetic field-controlled cell sorting area were provided on both the first flow channel and the second flow channel, at or just below the first and second intersection points shown above, so as to manipulate the flow of magnetically-labeled particles traveling therethrough. – Examiner further notes that the claim requires the magnetic field-controlled cell sorting area as provided “on” the first/second flow channels. As such, the claim merely requires the area be in contact with the channels, and not necessarily within them.)
the first fluorescence detection area is located on the sample channel; and the second fluorescence detection area is located on the target cell channel (Fig. 1A shows the “detection laser”, as discussed in paras. [0174-0175] as being used for fluorescence detection, as being on the sample channel; and the “further purification and analysis area”; as discussed in paras. [0297-0300] as being used for fluorescence detection, is further shown by the figure as being on the target cell channel. – Further, Fig. 18A shows an embodiment where the “further purification and analysis area” comprises a second sorting junction having the second detection laser/area for performing measurements and further sorting, as opposed to the alternative of a chamber as in Fig. 1A.)
a sample inlet of the sample channel and sample inlets of the two sheath fluid channels are connected to an injector and corresponding injection pumps respectively to provide power for a solution to flow in the chip ([0162]: “The labeled fluid sample can be injected into the top channel of the microfluidic chip using a syringe pump (FIG. 4A). Two side channels, where buffer flows through, can be used to control the active sorting step. Two ports are located on the right-side channel, and both are connected to a pressurized buffer source.” – [0167]: “In some aspects, the flow can be delivered by, for example, methods and devices that induce hydrodynamic fluidic pressure, which includes but is not limited to those that operate on the basis of mechanical principles (e.g., external syringe pumps)...”);
a sample outlet of the waste fluid channel is connected to a special collection bottle for waste fluid, which is used for collecting cells not required for sorting as well as excess cell waste fluid ([0261]: “Non-target cells can pass through such an output channel to a collection vial or to a waste receptacle”);
a sample outlet of the target cell channel is connected to a special bottle for target cells, which is used for collecting a solution containing the target cells (See paras. [0258-0271] “particle capture and detection” – see also Fig. 29A which shows particle collection after passing through the filter region, wherein fluid dripping as the “particle collection after retention” must necessarily comprise a container for collecting the dripping fluid, as one of ordinary skill in the art would readily recognize that one would not merely allow the fluid to spill onto a laboratory benchtop. – Further, while the containers/collections discussed by Chiu are not specifically described as “special bottles” one of ordinary skill in the art would recognize that any reservoir for collecting an analyte of interest would be an obvious alternative to a bottle, and wherein if the device were used for cell sorting, one of ordinary skill in the art would find it obvious to use a cell culture bottle, which is used throughout the art of cell culture/sorting given their specific design for culturing and maintaining cells such as inner wall surface treatment, vented caps for airflow, a flat bottom for even distribution, etc.),
as in Claim 1.
Further regarding Claim 1, Chiu does not specifically teach the microfluidic sorting device discussed above wherein the cell sorting area comprises one magnetron/magnet; the magnetron/magnet is controlled by the magnetic field control system to move back and forth on the first flow channel and the second flow channel so as to control a flow direction of a sample, as in Claim 1. – See further the 35 USC 112 section above regarding “magnetron/magnet”.
However, Chang-Yen teaches a respective microfluidic device ([0006]) wherein a magnet is controlled by a magnetic field control system to move back and forth across positions/channels of downstream trapping regions, so as to effectively trap and sort species of interest (Figs. 2B-C and [0057]: “As the cam actuator 231 rotates in the direction shown, a cam lobe in cam 233 engages a push member 255 connected to a first magnet 243. As actuator 231 continues to rotate, cam 233 pushes magnet 243 into position under a downstream portion of trapping region 253.”) – It is further noted that when the sorting region of Chang-Yen having moving magnets is applied to the sorting area of Chiu having an electromagnet, the magnets of Chang-Yen serve to move back and forth across the channels of Chiu, so as to affect the flow and channel-based sorting effect as similarly sought in Chang-Yen, given that Chiu merely uses an electromagnet instead of an actuatable magnet to achieve a same effect.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the microfluidic sorting device of Chiu such that the cell sorting area comprises one magnetron/magnet; the magnetron/magnet is controlled by the magnetic field control system to move back and forth on the first flow channel and the second flow channel so as to control a flow direction of a sample, such as suggested by Chang-Yen, given that one of ordinary skill int the art would recognize an electromagnet and a physically actuatable magnet to be mere alternatives of one another which serve the identical purpose of providing a variable magnetic field to direct a fluid flow containing magnetic particles; and would have a reasonable expectation of success therein.
Further regarding Claim 1, Chiu does not specifically teach the microfluidic sorting device discussed above wherein when the magneton is located at the first flow channel, the sample channel communicates with the waste fluid channel, and when the magneton is located at the second flow channel, the sample channel communicates with the target cell channel, as in Claim 1. See further the 35 USC 112 section above regarding “magnetron/magnet” as well as the required channel “communication”.
However, given the discussion above regarding the obvious combination of Chiu and Chang-Yen so as to utilize physically actuatable magnets in Chiu as opposed to electromagnets, and given the further above discussion regarding aqueous cell-sorting being based on attractive forces between magnetically-labeled particles and magnetic field generators, as normally understood and utilized in the art, Chiu/Chang-yen inherently teaches the microfluidic sorting device discussed above wherein when the magneton is located at the first flow channel, the sample channel communicates with the waste fluid channel, and when the magneton is located at the second flow channel, the sample channel communicates with the target cell channel, given that this arrangement is the only possible option for achieving the attractive-based cell-sorting sought by both Chiu and Chang-yen and for directing flow to the first/second channels utilizing a physical magnet and magnetically-labeled particles.
Examiner further notes that the recitations “the sample channel communicates with the waste fluid channel” and “the sample channel communicates with the target cell channel” are drawn to conditional (“when the magneton is located at the first flow channel” and “when the magneton is located at the second flow channel”) process recitations that are both not necessitated by the claim and, as the claims are drawn to a device, such process recitations are not afforded patentable weight. "Apparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc. – MPEP 2114(II).
Regarding Claim 2, the prior art meets the limitations of Claim 1 as discussed above. Further, Chiu teaches the microfluidic sorting device discussed above wherein:
the injector connected to the sample inlet of the sample channel is filled with a pre-treated cell sample solution (Para. [0107] discusses labeling of the sample prior to injection into the device. Thus, as para. [0162] teaches “The labeled fluid sample can be injected into the top channel of the microfluidic chip using a syringe pump (FIG. 4A).”, the injector connected to the sample inlet of the sample channel is thereby filled with a pre-treated cell sample solution.); and
the injectors connected to the sample inlets of the two sheath fluid channels are filled with a corresponding sheath solution, cell buffer or culture solution (Fig. 1A shows a buffer solution flowing through the sheath fluid channels. Thus, the syringe pumps of said sheath fluid channels (discussed above) must thereby be filled with buffer solution.),
as in Claim 2.
Examiner further notes that the recitations drawn to “is/are filled with” are drawn to process recitations. As the claims are drawn to a device, such process recitations are not afforded patentable weight when the prior art device is capable of performing the claimed process. "Apparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc. – MPEP 2114(II). Applicant may wish to amend the claim with a recitation on the order of “wherein the injector comprises a sample/buffer/sheath solution contained therein” etc.
Regarding Claim 5, the prior art meets the limitations of Claim 1 as discussed above. Further, Chiu teaches the microfluidic sorting device discussed above wherein:
the first flow channel and the second flow channel are respectively provided with a limit groove at the first intersection point and the second intersection point for enabling the magneton to block a path to the target cell channel or the waste fluid channel (Figs. 3A-H show various arrangements of solenoid actuators, interpreted as limiting grooves – see the 35 USC 112 section above. Therein, Fig. 3C shows limiting grooves provided on both the first and second flow channels, at the first and second intersection points, where para. [0152] describes their functionality for sorting. – Examiner further notes that the recitation “at” the intersection point merely requires nearness to the intersection, given its Merriam-Webster Disctionary first definition of the term “at”: “used as a function word to indicate presence or occurrence in, on, or near”. – Examiner further notes the recitation “block a path to the target cell channel or the waste fluid channel” is drawn to a process recitation. As the claims are drawn to a device, such process recitation is not afforded patentable weight when the prior art device is capable of performing the claimed process. "Apparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc. – MPEP 2114(II). Herein, the solenoids of Chiu are fully capable of being activated by the moving magnets of the obvious combination of Chiu and Chang-Yen given that generic solenoids are capable of being magnetically affected by an external magnet to exert a force on the solenoid plunger.), as in Claim 5.
Regarding Claim 6, the prior art meets the limitations of Claim 1 as discussed above. Further, Chiu teaches the microfluidic sorting device discussed above wherein the chip device is made of a plastic material with chemical inertness, optical transparence, and biocompatibility ([0133] teaches the chip as being fabricated from PMMA, a plastic material that is chemically inert, optically transparent, and biocompatible.), as in Claim 6.
Regarding Claim 7, the prior art meets the limitations of Claim 6 as discussed above. Further, Chiu teaches the microfluidic sorting device discussed above wherein the material of the chip device comprises polydimethylsiloxane, PMMA, COC, and COP (In some aspects, an apparatus provided herein can comprise a flow channel or chamber enclosed by walls fabricated from materials including, but not limited to...polymethylmethacrylate (PMMA)...cyclic olefin copolymers (COC), cyclic olefin polymers (COP)...and combinations thereof.), as in Claim 7.
Regarding Claim 8, Chiu teaches a method for sorting fluorescently labeled cells by the microfluidic chip device based on the magnetic field-controlled fluorescently labeled cell sorting method according to Claim 1 (See Claim 1 rejected under 35 USC 103 over Chiu in view of Chang-Yen above.), comprising the following steps:
S1, during preparation of sample injection, the laser devices, the fluorescence detectors and the magnetic field control system are turned on, and then three sample injection pumps are enabled (While Chiu does not specifically teach “turning on the device” as essentially claimed, given that the device is discussed as actively providing power to various pumps, magnets, lasers, detectors, etc, the device must have inherently been turned on. Further, one of ordinary skill in the art would find it obvious to turn on the device before using it, given that none of the power-requiring subordinate elements of the device would perform the desired function discussed by Chiu if they were off and inactive. Further, as Applicant has not specifically described any steps associated with “preparation of sample injection”, any step involving the sample, including leaving the sample alone to incubate or continue to be preserved while the device is warmed up, reads on mere “sample preparation”.);
S2; during sample injection, a solution injected into the sample inlet of the sample channel is a pre-treated cell sample solution incubated by a fluorescence antibody ([0236]: “For instance, an exogenous fluorophore may be attached to a cell by targeting the exogenous fluorophore that is covalently bound to an antibody to a corresponding surface antigen of the cell.” – Further, para. [0107] discusses pre-treatment/labeling of the sample prior to its injection into the device.), and a solution injected into the sample inlet of each sheath fluid channel is a sheath fluid solution (Fig. 1A shows sheath/buffer fluid being injected into the device, further exemplified in Figs. 9A-C, which must necessarily have been injected through a sheath fluid inlet to be able to flow through the device as shown in Fig. 1A.);
S3, when the pre-treated sample solution flows through the first fluorescence detection area and the second fluorescence detection area, the laser and the fluorescence detector are able to detect the solution in sequence, a detection result is processed by a computer system and then fed back to the magnetic field control system controlled by the computer system, and the magnetic field control system is able to control a movement direction of the magneton in the magnetic field (Fig. 18 shows the first detection laser and the second detection laser as able to detect the solution in sequence (one after the other). Further, paras. [0117, 0147, 0239] describe magnetic-based separation, including magnetic activated cell sorting, as the separation procedure, and para. [0020] teaches a computer for controlling the separation procedure. Additionally, Chang-yen also teaches actuation of magnets by a computer based on data collected by the detector and fed into said computer, wherein one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to provide this computer automation so as to provide the overall functionality to the sought sorting system.);
S31, if no cell with a fluorescently-labelled signal is detected in the first fluorescence detection area, the magnetic field control system is able to control the magneton to move to the first flow channels to block a path to the target cell channel, thus enabling the sample solution to flow towards the sample outlet of the waste fluid channel and to be collected in the special bottle for waste fluid finally ([0166]: “A positive event can be detected by the first detection window. In this case, a DC voltage (e.g., 5V) can be applied to the solenoid to open the buffer flow from the buffer reservoir (e.g., No. 2). The decreased flow resistance of the buffer channel on the right side can generate a higher flow rate. The fluid flow can be pushed from the right side to the left to collect the positive aliquot (FIG. 4C). The aliquot can be collected and confirmed by the second detection window. In some aspects, the solenoid can be closed to switch the fluid flow back to the waste collection channel (FIG. 4D).” – Herein, one of ordinary skill in the art would find it obvious that when implemented with magnets, the device will similarly use its magnetic means to direct cells not displaying fluorescence to the waste, instead of solenoids, such as discussed in para. [0239] and further contemplated by Chang-yen.);
S32, if the cell with the fluorescently-labeled signal is detected in the first fluorescence detection area, the magnetic field control system is able to control the magneton to move to the second flow channel to block a path to the waste fluid channel, thus enabling the sample solution containing the target cells to flow towards the sample outlet of the target cell channel and to flow through the second fluorescence detection area to reconfirm whether the target cell detected by the first fluorescence detection area exists or not, if it is reconfirmed that the target cell is detected, the system controls the magneton to return to the first flow channel to block the path to the target cell channel ([0166]: “A positive event can be detected by the first detection window. In this case, a DC voltage (e.g., 5V) can be applied to the solenoid to open the buffer flow from the buffer reservoir (e.g., No. 2). The decreased flow resistance of the buffer channel on the right side can generate a higher flow rate. The fluid flow can be pushed from the right side to the left to collect the positive aliquot (FIG. 4C). The aliquot can be collected and confirmed by the second detection window. In some aspects, the solenoid can be closed to switch the fluid flow back to the waste collection channel (FIG. 4D).” – Herein, one of ordinary skill in the art would find it obvious that when implemented with magnets, the device will similarly use its magnetic means to direct cells positively displaying fluorescence to the collection chamber, instead of solenoids, such as discussed in para. [0239] and further contemplated by Chang-yen. – Further, paras. [0114, 0186, 0300] discuss a confirmatory laser and detector to confirm a measurement before performing a sorting operation: “the confirmatory laser can be used as a second detection method to control the accuracy of the eDAR sorting scheme”.); and
S33, repeating the step S31 and the step S32 (Fig. 18A shows a structure wherein repetitions of laser measurements and sorting operations are confirmed, thereby repeating the steps of S31 and S32.),
and finally performing collection in the special bottle for target cells to obtain the target cells (See paras. [0258-0271] “particle capture and detection” – see also Fig. 29A which shows particle collection after passing through the filter region, wherein fluid dripping as the “particle collection after retention” must necessarily comprise a container for collecting the dripping fluid, as one of ordinary skill in the art would readily recognize that one would not merely allow the fluid to spill onto a laboratory benchtop. – Further, while the containers/collections discussed by Chiu are not specifically described as “special bottles” one of ordinary skill in the art would recognize that any reservoir for collecting an analyte of interest would be an obvious alternative to a bottle, and wherein if the device were used for cell sorting, one of ordinary skill in the art would find it obvious to use a cell culture bottle, which is used throughout the art of cell culture/sorting given their specific design for culturing and maintaining cells such as inner wall surface treatment, vented caps for airflow, a flat bottom for even distribution, etc.),
as in Claim 8.
Regarding Claim 9, the prior art meets the limitations of Claim 8 as discussed above. Further, Chiu teaches the method discussed above wherein:
the injector connected to the sample inlet of the sample channel is filled with a pre-treated cell sample solution (Para. [0107] discusses labeling of the sample prior to injection into the device. Thus, as para. [0162] teaches “The labeled fluid sample can be injected into the top channel of the microfluidic chip using a syringe pump (FIG. 4A).”, the injector connected to the sample inlet of the sample channel is thereby filled with a pre-treated cell sample solution.); and
the injectors connected to the sample inlets of the two sheath fluid channels are filled with a corresponding sheath solution, cell buffer or culture solution (Fig. 1A shows a buffer solution flowing through the sheath fluid channels. Thus, the syringe pumps of said sheath fluid channels (discussed above) must thereby be filled with buffer solution.),
as in Claim 9.
Regarding Claim 12, the prior art meets the limitations of Claim 8 as discussed above. Further, Chiu teaches the method discussed above wherein:
the first flow channel and the second flow channel are respectively provided with a limit groove at the first intersection point and the second intersection point for enabling the magneton to block a path to the target cell channel or the waste fluid channel (Figs. 3A-H show various arrangements of solenoid actuators, interpreted as limiting grooves – see the 35 USC 112 section above. Therein, Fig. 3C shows limiting grooves provided on both the first and second flow channels, at the first and second intersection points, where para. [0152] describes their functionality for sorting. – Examiner further notes that the recitation “at” the intersection point merely requires nearness to the intersection, given its Merriam-Webster Disctionary first definition of the term “at”: “used as a function word to indicate presence or occurrence in, on, or near”. – Examiner further notes the recitation “block a path to the target cell channel or the waste fluid channel” is drawn to a process recitation. As the claims are drawn to a device, such process recitation is not afforded patentable weight when the prior art device is capable of performing the claimed process. "Apparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc. – MPEP 2114(II). Herein, the solenoids of Chiu are fully capable of being activated by the moving magnets of the obvious combination of Chiu and Chang-Yen given that generic solenoids are capable of being magnetically affected by an external magnet to exert a force on the solenoid plunger.), as in Claim 12.
Regarding Claim 13, the prior art meets the limitations of Claim 8 as discussed above. Further, Chiu teaches the method discussed above wherein the chip device is made of a plastic material with chemical inertness, optical transparence, and biocompatibility ([0133] teaches the chip as being fabricated from PMMA, a plastic material that is chemically inert, optically transparent, and biocompatible.), as in Claim 13.
Regarding Claim 14, the prior art meets the limitations of Claim 13 as discussed above. Further, Chiu teaches the method discussed above wherein the material of the chip device comprises polydimethylsiloxane, PMMA, COC, and COP (In some aspects, an apparatus provided herein can comprise a flow channel or chamber enclosed by walls fabricated from materials including, but not limited to...polymethylmethacrylate (PMMA)...cyclic olefin copolymers (COC), cyclic olefin polymers (COP)...and combinations thereof.), as in Claim 14.
Claims 3-4 and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Chiu in view of Chang-Yen, as applied to Claims 1-2, 5-9, and 12-14 above, and in further view of Fu et al. (Fu, Jing-Lin; et al., “Laser-Induced Fluorescence Detection System for Microfluidic Chips Based on an Orthogonal Optical Arrangement”, Anal. Chem. 2006, 78, 11, 3827–3834), hereinafter “Fu”.
Regarding Claim 3, the prior art meets the limitations of Claim 1 as discussed above. Further, Chiu/Chang-Yen teaches the microfluidic sorting device discussed above wherein:
the first fluorescence detection area and the second fluorescence area have the same structure, each comprising a laser device and a fluorescence detector (See paras. [0021, 0024] which give a same description of the fluorescence detection area, each comprising a laser device and detector such as further discussed in paras. [0174-0175], and Fig. 18A which shows a same arrangement of the first and second detection lasers. – See further the 35 USC 112 section above regarding “the same structure” antecedent basis, and note that requiring “a same structure” merely requires each to have a laser or detector.),
as in Claim 3.
Further regarding Claim 3, Chiu/Chang-Yen does not specifically teach the microfluidic sorting device discussed above wherein the laser device and the fluorescence detector are respectively located at two sides of the chip; and the fluorescence detector comprises an optical filter, as in Claim 3.
However, Fu teaches a respective, simple laser-based microfluidic detection system, wherein the laser device and the fluorescence detector are respectively located at two sides of the chip (Fig. 2 shows the laser and PMT detector as on two different sides of the chip, wherein the 90-degree arrangement shown is common in fluorescence measurement so as to minimize interference effects from the incident light.); and the fluorescence detector comprises an optical filter (Fig. 2 shows the LP and BP filters of the device, which select for only the specific fluorescent wavelengths of interest, as further discussed in the “Apparatus and Equipment” section.).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the device of Chiu/Chang-Yen wherein the laser device and the fluorescence detector are respectively located at two sides of the chip; and the fluorescence detector comprises an optical filter, such as suggested by Fu, so as to minimize interference effects from the incident light, and select for only the specific fluorescent wavelengths of interest, thereby improving measurement accuracy and precision; and would have a reasonable expectation of success therein.
Regarding Claim 4, the prior art meets the limitations of Claim 3 as discussed above. Further, as discussed above regarding Claim 3, the obvious combination of the microfluidic sorting device of Chiu/Chang-Yen with the optical filter of Fu provides a structure able to filter out non-fluorescence signals, and only the fluorescence is retained to enter the detector, as discussed in the “Apparatus and Equipment” and “Optimization of Filters” sections.
Therein, one of ordinary skill in the art would find it obvious and be motivated to provide such filter arrangement in the combination so as to select for only the specific fluorescent wavelengths of interest, thereby improving measurement accuracy and precision.
Regarding Claim 10, the prior art meets the limitations of Claim 8 as discussed above. Further, Chiu/Chang-Yen teaches the method discussed above wherein:
the first fluorescence detection area and the second fluorescence area have the same structure, each comprising a laser device and a fluorescence detector (See paras. [0021, 0024] which give a same description of the fluorescence detection area, each comprising a laser device and detector such as further discussed in paras. [0174-0175], and Fig. 18A which shows a same arrangement of the first and second detection lasers. – See further the 35 USC 112 section above regarding “the same structure” antecedent basis, and note that requiring “a same structure” merely requires each to have a laser or detector.),
as in Claim 10.
Further regarding Claim 10, Chiu/Chang-Yen does not specifically teach the method discussed above wherein the laser device and the fluorescence detector are respectively located at two sides of the chip; and the fluorescence detector comprises an optical filter, as in Claim 10.
However, Fu teaches a respective, simple laser-based microfluidic detection system, wherein the laser device and the fluorescence detector are respectively located at two sides of the chip (Fig. 2 shows the laser and PMT detector as on two different sides of the chip, wherein the 90-degree arrangement shown is common in fluorescence measurement so as to minimize interference effects from the incident light.); and the fluorescence detector comprises an optical filter (Fig. 2 shows the LP and BP filters of the device, which select for only the specific fluorescent wavelengths of interest, as further discussed in the “Apparatus and Equipment” section.).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the method of Chiu/Chang-Yen wherein the laser device and the fluorescence detector are respectively located at two sides of the chip; and the fluorescence detector comprises an optical filter, such as suggested by Fu, so as to minimize interference effects from the incident light, and select for only the specific fluorescent wavelengths of interest, thereby improving measurement accuracy and precision; and would have a reasonable expectation of success therein.
Regarding Claim 11, the prior art meets the limitations of Claim 10 as discussed above. Further, as discussed above regarding Claim 10, the obvious combination of the microfluidic sorting device of Chiu/Chang-Yen with the optical filter of Fu provides a method able to filter out non-fluorescence signals, and only the fluorescence is